Multicentre Placebo-controlled Double-blinded Phase II Study of Lenvatinib Efficacy in Patients With Locally Advanced or Metastatic GIST (Gastrointestinal Stromal Tumor) After Imatinib/Sunitinib Failure

NCT04193553 | Completed Phase 2 DMC

• 1 other identifier: ET18-291 - LENVAGIST
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 14

Brief Summary

The primary objective is to compare the efficacy of lenvatinib plus Best Supportive Care versus Placebo plus Best Supportive Care in the treatment of patients with advanced GIST, after failure of imatinib and sunitinib.

Conditions

Gastro Intestinal Stromal Tumour

Keywords

Gastro Intestinal Stromal Tumour; Locally advanced or metastatic; Tyrosine kinase inhibitors

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS, defined as the time from the date of randomisation to the date of the first documented radiological progression (RECIST 1.1) or death due to any cause. PFS will be estimated using the Kaplan-Meier method and will be described in terms of median PFS per arm, and hazard ratio for progression between the 2 arms. Associated 2-sided 95% CI for the estimates will be provided.

  Up to 30 months

Secondary Outcomes (6)

• Overall Survival (OS)

  Up to 30 months

• Objective Response Rate (ORR) for patient in the blinded part of the study

  Up to 30 months

• Best Overall Response (BOR) for patient in the blinded part of the study

  Up to 30 months

• Quality of Life (QoL) for patient in the blinded part of the study

  Up to 30 months

• Patient's tolerance to treatment

  Up to 30 months

Other Outcomes (3)

• Mutation profile : KIT

  Inclusion

• Mutation profile: PDGFR

  Inclusion

• Pharmacokinetic properties of lenvatinib for patient in the blinded part of the study

  Inclusion, Day 1 of cycles 2, 3, 4, 5, up to 12 months (28 days cycle)

Study Arms (2)

Lenvatinib + Best Supportive Care

EXPERIMENTAL

Drug: Lenvatinib; Other: Best supportive care

Placebo + Best Supportive Care

PLACEBO COMPARATOR

Drug: Placebo; Other: Best supportive care

Interventions

Lenvatinib DRUG

Lenvatinib will be administered continuously but patient's follow-up visits will be scheduled monthly. The starting dose of study treatment is 24mg, once daily, at the same time. Recommendations for dose reductions will be respected according to BI Lenvatinib. If a patient misses a dose, and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time of administration. Study treatments will be continued until a treatment discontinuation criteria is met.

Lenvatinib + Best Supportive Care

Placebo DRUG

Placebo will be administered continuously but patient's follow-up visits will be scheduled monthly. The starting dose of study treatment is 24mg, once daily, at the same time. Recommendations for placebo dose reductions are the same as for Lenvatinib. If a patient misses a dose, and it cannot be taken within 12 hours, then that dose should be skipped and the next dose should be taken at the usual time of administration. Study treatments will be continued until a treatment discontinuation criteria is met. In case disease progression, patients in control arm could switch in the Lenvatinib + BSC arm.

Placebo + Best Supportive Care

Best supportive care OTHER

At any time during the study, patients should receive best supportive care. Best Supportive care as medically indicated for the patient's well-being may be prescribed at the investigator's discretion. Based on the patient's condition, it may consist (but not limited) of analgesics, antibiotics, steroids, blood transfusion, antiemetics, antidepressants/anxiolytics, nutritional counselling, psychological support, palliative radiotherapy…

Lenvatinib + Best Supportive Care; Placebo + Best Supportive Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. Male or female ≥ 18 years at the day of consenting to the study.
• I2. Patient must have histologically confirmed diagnosis of GIST.
• I3. Disease must be locally advanced or metastatic.
• I4. Patient who failed (disease progression and/or intolerance) previously at least to imatinib and sunitinib.
• Nota Bene: patients with more than 2 previous anticancer treatments are eligible.
• I5. Patient must have evidence of measurable disease as per the RECIST version 1.1 (Appendix 2).
• I6. Patient must have documented disease progression. I7. ECOG performance status 0, 1 or 2 (Appendix 3).
• I8. Patient must have normal organ and bone marrow function as defined below:
• Hematologic
• Absolute neutrophil count (ANC) ≥ 1.5 Gi/L
• Haemoglobin ≥ 9 g/dl (5.6 mmol/l) (subjects may not have had a transfusion within 7 days of screening assessment)
• Platelets ≥ 100 Gi/l
• Coagulation panel
• Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN)
• Partial thromboplastin time (PTT) ≤ 1.2 X ULN Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.

You may not qualify if:

• E1. Patient with a documented mutation in PDGFRA exon 18 (D842V substitution).
• E2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesions with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel.
• E3. Any active/uncontrolled infection, including known infection with HIV, Hepatitis B or Hepatitis C.
• E4. Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• E5. History of any one or more of the following cardiovascular conditions within the past 6 months prior to the first dose of study drug:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (14)

Centre Antoine LACASSAGNE

Nice, Alpes-Maritimes, 06189, France

Location

Hopital de La Timone

Marseille, Bouches Du Rhône, 13385, France

Location

Institut Paoli Calmette

Marseille, Bouches-du-Rhône, 13273, France

Location

Centre Georges-François Leclerc

Dijon, Bourgogne-Franche-Comté, 21079, France

Location

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, Haute-Garonne, 31059, France

Location

Centre Oscar LAMBRET

Lille, Hauts-de-France, 59020, France

Location

Centre Eugène Marquis

Rennes, Ille-et-Vilaine, 44229, France

Location

ICO Centre René Gauducheau

Saint-Herblain, Loire-Atlantique, 44805, France

Location

CHU de Reims

Reims, Marne, 51000, France

Location

Institut de Cancérologie de Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

Location

Centre Léon Bérard

Lyon, Rhône, 69373, France

Location

Institut Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

Location

CHU Poitiers

Poitiers, Vienne, 86021, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Axel LE CESNE, Ph

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 10, 2019
• Study Start: January 17, 2020
• Primary Completion: January 30, 2024
• Study Completion: April 26, 2024
• Last Updated: June 18, 2024

Record last verified: 2024-04

Locations

FR (14)